Design and synthesis of orally bioavailable benzimidazoles as Raf kinase inhibitors.
A series of arylaminobenzimidazoles was designed and synthesized as Raf kinase inhibitors. Exploration of the structure-activity relationship resulted in compounds that are potent in vitro and show desirable in vivo properties.
Ramurthy
Savithri
S
Novartis Institutes for Biomedical Research, 4560 Horton Street, Emeryville, California 94608, USA. savithri.ramurthy@novartis.com
Subramanian
Sharadha
S
Aikawa
Mina
M
Amiri
Payman
P
Costales
Abran
A
Dove
Jeff
J
Fong
Susan
S
Jansen
Johanna M
JM
Levine
Barry
B
Ma
Sylvia
S
McBride
Christopher M
CM
Michaelian
Jonah
J
Pick
Teresa
T
Poon
Daniel J
DJ
Girish
Sandhya
S
Shafer
Cynthia M
CM
Stuart
Darrin
D
Sung
Leonard
L
Renhowe
Paul A
PA
D000284:Administration, Oral; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays; D048490:raf Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D048490:raf Kinases